PB2654: RARE BLEEDING DISORDERS: LONG-TERM EXPERIENCE FROM A HEMOPHILIA CENTER
Authors: Antonios Meimaridis, Sofia Chissan, Nikolaos Kotsiou, Eleni Gavriilaki, Eleni Moka, Sofia Vakalopoulou
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Coagulation factor deficiencies I, II, V, VII, X, XI, XIII and V+VIII are rare inherited disorders that cause lifelong bleeding diathesis. These disorders are mostly transmitted as autosomal recessive conditions and are clinically manifested in homozygous or double heterozygous states. Their incidence worldwide ranges from 1/500,000 to 1/2 - 3,000,000 and the prevalence is higher in areas with tradition of consanguineous marriages. Aims: We aimed to record demographic data, clinical manifestations, laboratory findings and treatment of patients with rare deficiencies of coagulation factors in order to enhance understanding of the pathophysiology, clinical symptoms, laboratory findings and management of these disorders. Methods: In this retrospective study, we analyzed consecutive medical records of 60 adult patients diagnosed with rare hereditary deficiencies of coagulation factors over the last 20 years. 23 men and 37 women who were listed in the Hemophilia Center of Northern Greece were examined. The study focused on patients with the following coagulation factor deficiencies: 12 patients with afibrinogenemia or hypofibrinogenemia 3 patients with factor V deficiency 33 patients with factor VII deficiency 5 patients with factor X deficiency 6 patients with factor XI deficiency 1 patient with factor XIII deficiency Results: Diagnosis of patients was based on factor activity levels as part of bleeding diathesis testing, abnormal coagulation results in routine examinations, family history of bleeding, or pre-operative testing in asymptomatic patients. Molecular diagnosis was limited to patients with afibrinogenemia. Mucosal bleedings and hemorrhages during surgical procedures were the most common bleeding events reported by almost all patients. Patients with fibrinogen, factor X and XIII deficiencies suffered from more severe bleeding manifestations. Women with fibrinogen deficiency and factor VII, X, XI, and XIII deficiencies reported menorrhagia, parturition bleeds, or spontaneous abortions. Thrombotic events were reported in a female patient with afibrinogenemia. Association between severity of the hemorrhagic symptoms and factor activity levels was heterogeneous. While patients with fibrinogen, factor X and factor XIII deficiencies showed a strong correlation between factor levels and the severity of hemorrhagic phenotype, no clear correlation was found between factor levels and hemorrhagic manifestations in patients with factors V, VII, and XI deficiency. Management of patients in the study included administration of fresh frozen plasma (FFP), plasma - derived fibrinogen, factor X and factor XI concentrates and recombinant activated factor VII (rFVIIa). Prophylactic treatment was given to patients with afibrinogenemia and factor XIII deficiency. However, replacement therapy has been associated with complications such as anaphylactic reactions at FFP transfusion and infection with hepatitis C and B viruses. Summary/Conclusion Our real-world study enrolled patients who were referred or directed to the Hemophiliac Center of Northern Greece but this group accounts only for a small fraction (14.6%) of patients with rare coagulation factor deficiencies recorded in the Greek population. This undersized proportion, compared to the regional population, indicates that numerous patients remain undiagnosed. Findings of this research corroborate those reported in the literature concerning clinical manifestations, diagnosis and management strategies. Keywords: Coagulation factors, Fibrinogen, Bleeding disorder